Concentration determination apparatus and concentration determination method

ABSTRACT

A first temperature sensor is formed in a first measurement area so that a measurement surface thereof is exposed to an inner surface of a liquid tank (a storage body). The first temperature sensor can detect a temperature of liquid injected into the liquid tank. Further, a first input part is formed in the first measurement area so that an output surface thereof is exposed to the inner surface of the liquid tank.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention relates to a concentration determination apparatusand a concentration determination method that are suitable for adetermination of a concentration of a measured component contained in aliving body tissue, particularly, a concentration of glucose containedin skin.

This application claims priority to and the benefits of Japanese PatentApplication No. 2011-137316 filed on Jun. 21, 2011, the disclosure ofwhich being incorporated herein by reference.

2. Related Art

Traditionally, measurement of a blood sugar level has been performed bytaking a blood sample from, for example, a fingertip and measuringenzyme activity for glucose in the blood. However, in such a method ofmeasuring a blood sugar level, blood must be collected from, forexample, the fingertip to perform the measurement and taking the bloodsample requires effort and is painful. Also, a measurement tip foradhering blood is necessary. Accordingly, there is a need for anon-invasive blood sugar level measurement method that does not requirethat a blood sample be taken.

For example, an apparatus for measuring a glucose concentration in aliving body disclosed in Japanese Patent Application, First PublicationNo. 2001-29972 has been known as an example of realizing thenon-invasive blood sugar level measurement as described above. Ingeneral, an apparatus in which, when near-infrared spectroscopicanalysis of a solution or a sample having high moisture content isperformed, for example, a shift of a spectrum of the sample due totemperature change is greatly changed, similar to a spectrum of water,and an influence of temperature is not negligible in quantitativeanalysis has been known. In the measurement apparatus disclosed inJapanese Patent Application, First Publication No. 2001-299727, when aglucose concentration is measured, a temperature of a target tissue iscontrolled to have a constant value by a temperature control means,thereby quantifying the target component with higher measurementaccuracy.

Further, for example, a double-beam Fourier transform infraredspectroscopic method for detecting a specific component in a samplehaving low transmittance disclosed in Published Japanese Translation ofa PCT application No. 2003-535329 has been known. In the above-describedinfrared spectroscopic analysis, arranging a material containing wateras a reference material for a measuring object is shown. Accordingly,the target component may be quantified with higher measurement accuracy.

SUMMARY OF THE INVENTION

However, in the measurement apparatus disclosed in Japanese PatentApplication, First Publication No. 2001-299727, there is no referencematerial for a measuring object when measurement is performed.Accordingly, a deviation (error) is easily generated in a measurementvalue measured by the above measurement apparatus. Further, when aconcentration of a very small amount of component is detected, it isnecessary to detect a small absorbance from a great absorbancemeasurement value. Accordingly, it is difficult to increase themeasurement accuracy, and a large dynamic range is necessary formeasurement with high accuracy. Further, the measurement apparatusincludes a temperature control means formed on a measurement surface.However, for example, when a glucose concentration is measured in aliving body tissue, it is difficult to secure temperature controlaccuracy in the order of 0.001° C. necessary for the measurement.

Further, in the infrared spectroscopic analysis method disclosed inPublished Japanese Translation of a PCT application No. 2003-535329, areference material for a measuring object is arranged. However, whenthere is a difference in temperature between the reference material anda sample of the measuring object, a spectrum is shifted due to atemperature change, which causes an error in the measurement value. As aresult, in the infrared spectroscopic analysis method disclosed inPublished Japanese Translation of a PCT application No. 2003-535329, itis also difficult to perform quantification with high accuracy.

The present invention has been made in view of the above-describedproblem, and one aspect of the present invention relates to aconcentration determination apparatus capable of performing highlyaccurate measurement and rapid measurement of a concentration of ameasured component contained in a living body tissue without beingaffected by a temperature change in a measurement environment.

Further, one aspect of the present invention relates to a concentrationdetermination method by which highly accurate measurement and rapidmeasurement of a concentration of a measured component contained in aliving body tissue can be performed without being affected by atemperature change in a measurement environment.

In order to resolve the above-described problem, some aspects of thepresent invention provide the following concentration determinationapparatus and method.

The concentration determination apparatus of the present inventionincludes a storage body for holding liquid, a temperature control plateconstituting the storage body and having one surface forming a closelycontacted surface which is closely contacted to a living body tissue andanother surface forming a liquid contact surface brought into contactwith the liquid, a first input part for causing a first incident lightto be incident on the storage body, a first light receiving part forreceiving a reference light transmitted through the liquid from thefirst input part, a second input part for causing a second incidentlight to be incident on the living body tissue, a second light receivingpart for receiving a measurement light from the second input part viathe living body tissue, a temperature detection device for detecting atemperature of the liquid and a temperature of the living body tissue,an absorbance calculation device for detecting an absorbance of theliquid and an absorbance of the living body tissue based on a lightintensity of the reference light and a light intensity of themeasurement light, and a concentration calculation device for comparingthe absorbance of the liquid with the absorbance of the living bodytissue and calculating a concentration of a measured component containedin the living body tissue.

According to the above-described concentration determination apparatus,the liquid that is the reference material is stored in the storage body,which stores the liquid, and the absorbance of the reference lighttransmitted through the liquid is referenced with respect to theabsorbance of the measurement light back-scattered from the living bodytissue that is the measuring object, thereby obtaining an accurateabsorbance without being affected by the liquid (e.g., water) containedin the measuring object,

Further, the temperature control plate having excellent thermalconductivity is formed in at least part of the storage body thatcontacts with the measuring object, and the temperature of the liquid inthe storage body rises due to heat of the living body tissue that is themeasuring object through the temperature control plate, such that thetemperature of the liquid can be rapidly the same as the temperature ofthe living body tissue. Accordingly, even when the liquid is liquidwhose absorption is sensitive to a temperature, the temperature of theliquid that is the reference material is the same as the temperature ofthe living body tissue that is the measuring object (i.e., a thermalequilibrium state) and then the absorbance is measured. Thus, it ispossible to eliminate a measurement error caused by an influence of theliquid in the living body tissue due to a temperature change and performan accurate concentration determination for the measured material.

The liquid is water or liquid corresponding to body fluid whosecomponent configuration is obvious. Also, the liquid may be a liquidhaving a scattering characteristic.

The temperature control plate may include a thermal conductor forcausing the body temperature of the living body tissue and the liquidtemperature of the liquid to be heat-exchanged with each other.

The storage body may further include a reflector for reflecting thefirst incident light incident from the first input part to the firstlight receiving part. Also, the concentration determination apparatusmay include a light source unit including a plurality of light sources.

The storage body may further include a temperature control device forheating or cooling the liquid.

The concentration determination apparatus further includes a lightsource unit including a light source, and a spectroscopic device fordividing light irradiated from the light source toward the first inputpart and the second input part.

The concentration determination apparatus further includes one lightreceiving element for measuring both the light intensity of thereference light incident on the first light receiving part and the lightintensity of the measurement light incident on the second lightreceiving part.

An optical path length for the reference light from the first input partto the first light receiving part may be the same as an optical pathlength for the measurement light from the second input part to thesecond light receiving part.

A concentration determination method of the present invention is aconcentration determination method using a concentration determinationapparatus comprising a storage body for holding liquid, a temperaturecontrol plate constituting the storage body and having one surfaceforming a closely contacted surface which is closely contacted to aliving body tissue and the other surface forming a liquid contactsurface brought into contact with the liquid, a first input part forcausing a first incident light to be incident on the storage body, afirst light receiving part for receiving a reference light transmittedthrough the liquid from the first input part, a second input part forcausing a second incident light to be incident on the living bodytissue, a second light receiving part for receiving a measurement lightfrom the second input part via the living body tissue, a temperaturedetection device for detecting a temperature of the liquid and atemperature of the living body tissue, an absorbance calculation devicefor detecting an absorbance of the liquid and an absorbance of theliving body tissue based on a light intensity of the reference light anda light intensity of the measurement light, and a concentrationcalculation device for comparing the absorbance of the liquid with theabsorbance of the living body tissue and calculating a concentration ofa measured component contained in the living body tissue, wherein: themeasurement light is light from the second incident light back-scatteredin the living body tissue, and the method comprises processes of:

equilibrating the temperatures so that a difference between the bodytemperature of the living body tissue and the liquid temperature of theliquid is within 0.1° C.; measuring the absorbance of the liquid basedon the light intensity of the reference light; measuring the absorbanceof the living body tissue based on the light intensity of themeasurement light; and using the absorbance of the liquid as a referenceand calculating the concentration of the measured component contained inthe living body tissue from the absorbance of the living body tissue.

The first incident light and the second incident light may be shortpulsed lights.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic block diagram showing a configuration of aconcentration determination apparatus;

FIG. 2A is a cross-sectional view of a body part taken along line A-A inFIG

FIG. 2B is a plan view of the body part in FIG. 1 when viewed fromabove;

FIG. 3 is a configuration diagram showing a large flow of concentrationdetermination;

FIG. 4 is a schematic view of a skin tissue of a human andback-scattering of an incident light;

FIG. 5 is a graph showing an example of an optical propagation pathlength distribution of respective layers of a living body tissue (skin);

FIG. 6 is a graph showing an example of a time-resolved waveform;

FIG. 7 is a graph showing absorption spectra of main components of theskin;

FIG. 8 is a diagram showing a configuration of a concentrationdetermination apparatus in a second embodiment;

FIG. 9 is a diagram shows a configuration of a concentrationdetermination apparatus in a third embodiment;

FIG. 10A is a cross-sectional view of a body part in a concentrationdetermination apparatus in a fourth embodiment;

FIG. 10B is a plan view of the body part in the concentrationdetermination apparatus of the fourth embodiment when viewed from above;and

FIG. 11 is a cross-sectional view of a body part in a concentrationdetermination apparatus in a fifth embodiment.

EMBODIMENTS OF THE INVENTION

Hereinafter, embodiments of a concentration determination apparatus anda concentration determination method according to the present inventionwill be described with reference to the accompanying drawings. Further,the following embodiments will be described in detail for betterunderstanding of the present invention and do not limit the presentinvention unless mentioned otherwise. In the drawings used in thefollowing description, for convenience, primary parts may be enlargedfor easy understanding of characteristics of the present invention, andthe dimensions of components may not be the same as actual ones.

First Embodiment

FIG. 1 is a schematic block diagram showing a configuration of a bloodsugar level measurement apparatus, which is an example of aconcentration determination apparatus.

The blood sugar level measurement apparatus (a concentrationdetermination apparatus) 100 includes a measurement device 110, a lightsource unit 120, a light receiving element 130, a control unit 140, anoperational unit 150, and a concentration display unit 160.

The measurement device 110 is mounted on, for example, an arm part of ahuman body and then used. The measurement device 110 includes a bodypart 111, and a band (fixing member) 112 for closely contacting andfixing the body part 111 to the arm part when glucose, which is ameasuring object material, is measured.

The body part 111 has, for example, an overall appearance as a thincube. In the body part 111, a first measurement area 113 a is formed atone side from near a center of the body part 111 and a secondmeasurement area 113 b is formed at the other side.

FIG. 2A is a cross-sectional view taken along line A-A of the body part111 shown in FIG. 1. FIG. 2B is a plan view of the body part 111 shownin FIG. 1 when viewed from above.

For example, a hollow liquid tank (storage body) 114 that liquid(reference material) Q can be injected into and held in is formed in thefirst measurement area 113 a. An opening 114 a through which the liquid(reference material) Q is injected into or discharged from the liquidtank 114, and a stopper 114 b for blocking the opening 114 a areincluded in the first measurement area 113 a.

A temperature control plate 170 is formed at a side of a bottom surfaceamong wall surfaces partitioning the liquid tank (storage body) 114. Inthe temperature control plate 170, one surface thereof forms a closelycontacted surface. 170 a that is closely contacted to a surface of theliving body tissue (e.g., the arm part W of the human body) that is themeasuring object upon measurement, and the other surface thereof forms aliquid contact surface 170 b that contacts the liquid (the referencematerial) Q. The temperature control plate 170 may be formed of athermal conductor for efficiently heat-exchanging a body temperature ofthe living body tissue and a liquid temperature of the liquid Q witheach other, such as a copper plate, an aluminum plate, or the like.

A first temperature sensor 115 a is formed in the first measurement area113 a so that a measurement surface thereof is exposed to an innersurface of the liquid tank (storage body) 114. The first temperaturesensor 115 a detects a temperature T1 of the liquid Q injected into theliquid tank 114.

A first input part 116 is formed in the first measurement area 113 a sothat an output surface 116 a of the first input part 116 is exposed tothe inner surface of the liquid tank 114. The first input part 116 maybe, for example, a light guiding member (a light guide) formed oftransparent resin. The first input part 116 is optically connected to alight source 122 via a spectral unit (spectroscopic device) 121 of thelight source unit 120. For example, the spectral unit 121 and the firstinput part 116 may be connected to each other by an optical fiber.

In the first measurement area 113 a, a first light receiving part 117 isformed so that an input surface 117 a thereof is exposed to the innersurface of the liquid tank 114. The first light receiving part 117 isformed in a position in which the input surface 117 a faces the outputsurface 116 a of the first input part 116. Accordingly, light outputfrom the output surface 116 a proceeds along one surface of the bodypart 111, for example, the liquid contact surface 170 b, is transmittedthrough the liquid Q stored in the liquid tank 114, and is incident onthe facing input surface 117 a as a reference light L1.

The first light receiving part 117, for example, may be a light guidingmember (light guide) formed of transparent resin. The first lightreceiving part 117 is optically connected to the light receiving element130. The light receiving element 130 and the first light receiving part117 are connected to each other, for example, by an optical fiber.

In the second measurement area 113 b, a second temperature sensor 115 bexposed to the bottom surface ilia of the body part 111 is formed to bebrought into contact with the arm part W of the human body fixed to theband (fixing member) 112 upon measurement. The second temperature sensor115 b detects a surface temperature (a body temperature) T2 of the armpart W, which is the living body tissue of the measuring object. Atemperature sensor 115 includes the second temperature sensor 115 b andthe first temperature sensor 115 a.

A second input part 118 is formed in the second measurement area 113 bso that an output surface 118 a thereof is exposed to the bottom surface111 a of the body part 111. The second input part 118 may be, forexample, a light guiding member (light guide) formed of transparentresin. The second input part 118 is optically connected to the lightsource 122 via the spectral unit 121 of the light source unit 120. Thespectral unit 121 and the second input part 118 may be connected to eachother, for example, by an optical fiber.

A second light receiving part 119 is formed in the second measurementarea 113 b so that an input surface 119 a thereof is exposed to thebottom surface 111 a of the body part 111. The input surface 119 a ofthe second light receiving part 119 and the output surface 118 a of thesecond input part 118 may be formed to extend on the same surface alongthe bottom surface 111 a. Light output from the output surface 118 a isincident on the arm part W, which is the living body tissue of themeasuring object, output from the arm part W by back-scattering, andincident on the input surface 119 a parallel to the output surface 118 aas a measurement light L2.

The second light receiving part 119 may be, for example, a light guidingmember (light guide) formed of transparent resin. The second lightreceiving part 119 is optically connected to the light receiving element130. The light receiving element 130 and the second light receiving part117 may be connected to each other, for example, by an optical fiber.

The description will be further given with reference to FIG. 1. Thelight source unit 120 includes the light source 122 and the spectralunit (a spectroscopic device) 121. The light source 122 may be, forexample, a laser light source that can irradiate a short pulsed lighthaving a specific wavelength. Further, the short pulsed light refers toa pulsed light having a pulse width of about 100 psec or less. A pulsedlight having a pulse width ranging from 0.1 psec to a few psec may beused as the short pulsed light.

The spectral unit (spectroscopic device) 121 includes, for example, anoptical path switching device. The spectroscopic unit causes a lightirradiated from the light source 122 to be selectively incident on thefirst input part 116 or the second input part 118. The spectral unit(spectroscopic device) 121 may include a prism, a half mirror, or thelike, and may cause the light irradiated from the light source 122 to bedivided and incident on the first input part 116 and the second inputpart 118.

The light receiving element 130 includes, for example, a photodiode. Thelight receiving element 130 transmits a light intensity signal accordingto a light intensity of the reference light L1 output from the firstlight receiving part 117 or the measurement light L2 output from thesecond light receiving part 119, to the control unit 140.

A mechanism for selectively receiving any one of the reference light L1output from the first light receiving part 117 and the measurement lightL2 output from the second light receiving part 119 under control of thecontrol unit 140 may be further included.

The control unit 140 is connected to the light source unit 120, thetemperature sensor 115, the light receiving element 130, and theoperational unit 150. The control unit 140 includes an input/outputcircuit for transmitting and receiving signals, control information orthe like to and from such units.

The operational unit 150 includes a CPU, a memory and the like, and maybe, for example, a personal computer (PC). The operational unit 150calculates a concentration of the measuring object, for example, basedon light intensity information output from the control unit 140 orreference data stored in the memory in advance according to apredetermined procedure. Further, a detailed configuration of theoperational unit 150 and the concentration calculation will be describedlater.

The concentration display unit 160 may be, for example, a display, aprinter or the like. The concentration display unit 160 displays orprints the concentration of the measuring object calculated by theoperational unit 150.

The spectral unit (spectroscopic device) 121 includes, for example, adiffraction grating. The spectroscopic unit may divide light irradiatedfrom the light source 122 into wavelengths. A light having thewavelength selected by the spectral unit 121 is simultaneously incidenton the first input part 116 and the second input part 118. When dataacquisition for a plurality of wavelengths is necessary, lights havingthe divided different wavelengths may be sequentially incident on thefirst input part 116 and the second input part 118.

In another configuration example of the blood sugar level measurementapparatus (concentration determination apparatus) 100 shown in FIG. 1,the light source unit may include a plurality of light sources, forexample, two light sources. A light emitted from one light source may besimultaneously incident on the first input part 116 and the second inputpart 118 and data acquisition may be performed. Then, a light emittedfrom the second light source may be simultaneously incident on the firstinput part 116 and the second input part 118 and data acquisition may beperformed. Accordingly, even when the light source that emits a shortpulsed light is a general light source for outputting a singlewavelength light, it is possible to cause different wavelength lights tobe incident on the first and second input parts with a simpleconfiguration having no spectral unit (spectroscopic device) 121 bycombining a plurality of light sources having different outputwavelengths.

A concentration determination method using the blood sugar levelmeasurement apparatus (the concentration determination apparatus) havingthe above configuration and an operation of the blood sugar levelmeasurement apparatus will be described in detail.

First, prior to measurement of the blood sugar level, the user opens thestopper 114 b of the liquid tank 114 formed in the body part 111 of theblood sugar level measurement apparatus 100 to cause the opening 114 ato be exposed. Also, the user fills the liquid tank 114 with liquid as areference material, specifically, water, from the opening 114 a and thenblocks the opening 114 a with the stopper 114 b. Further, this liquidmay be body fluid collected in advance, liquid corresponding to bodyfluid whose components are obvious, a physiological salt solution,liquid having a scattering characteristic, or the like, as well as thewater.

Next, the user closely contacts the bottom surface 111 a of the bodypart 111 to a measurement place, for example, the arm part W, and fixesthe body part 111 to the arm part using the band (fixing member) 112.Accordingly, the closely contacted surface 170 a of the temperaturecontrol plate 170 is closely contacted to the surface of the arm part W.Also, the user waits a predetermined time, specifically, until a bodytemperature of the arm part W in contact with the closely contactedsurface 170 a of the temperature control plate 170 and a liquidtemperature of the liquid Q in contact with the liquid contact surface170 b of the temperature control plate 170 are heat-exchanged throughthe temperature control plate 170 and then the liquid temperature of theliquid Q is heated or cooled to be the same as the body temperature, ina state in which the user causes the closely contacted surface 170 a tobe closely contacted to the arm part W.

The temperature of the liquid Q and the body temperature of the arm partare always measured by the temperature sensor 115 while the user iswaiting. Specifically, temperature signals from the temperature sensor115 a for measuring the temperature of the liquid Q in the liquid tank114 and the temperature sensor 115 b closely contacted to the surface ofthe arm part W to measure the body temperature of the human body (thetemperature of the skin surface that is the measurement place) arecontinuously input to the control unit 140. Also, if the temperaturesignal from the temperature sensor 115 a and the temperature signal fromthe temperature sensor 115 b become the same as each other in apredetermined range, it is determined that the temperature of the liquidQ in the liquid tank 114 rises due to the body temperature of the humanbody and the temperature of the liquid Q and the temperature of the skinsurface have become the same as each other.

After the temperature of the liquid Q has become the same as that of theskin surface, the process proceeds to a measurement (determination)process for a blood sugar level. In the measurement (determination)process for a blood sugar level, a process of irradiating a short pulsedlight to the skin, which is the measuring object, to measure anabsorbance of the skin (a process of obtaining a measurement light), anda process of irradiating a short pulsed light to the liquid (water),which is a reference material, to measure an absorbance of the liquid (aprocess of obtaining a reference light) are performed with apredetermined time difference or simultaneously.

FIG. 3 is a configuration diagram showing an example of theconcentration determination, that is, a large flow of non-invasivelymeasuring a glucose concentration in body fluid present in the skin ofthe arm part of the human body. The light output from the light source122 is divided into two optical paths. In one optical path, the light isincident from the second input part 118 to the living body tissue thatis the measuring object, that is, the arm part W of the human body towhich the body part 111 has been fixed.

As shown in FIG. 4, skin tissue of a human is formed of three layers ofan epidermis, a dermis, and subcutaneous tissue. The epidermis is anoutermost thin layer having a thickness of 0.2 to 0.3 mm, and includes acorneous layer, a granular layer, a stratum spinosum, a bottom and thelike. The dermis is a layer having a thickness of 0.5 to 2 mm, which ispresent between the epidermis and the subcutaneous tissue. In thedermis, there are nerves, hair roots, sebaceous glands or sweat glands,hair follicles, blood vessels, and lymph nodes. The subcutaneous tissueis a layer having a thickness of 1 to 3 mm, which is present beneath thedermis. Most of the subcutaneous tissue is formed of subcutaneous fat.

Capillaries and the like are developed in the dermis, rapid materialmovement according to blood glucose occurs, and a glucose concentrationin the dermis is changed with blood glucose concentration (a blood sugarlevel). Therefore, the blood sugar level measurement apparatus 100measures an absorbance after transmission through the measuring objectby irradiating a light (a short pulsed light) from the second input part118 to the surface of the skin tissue and detecting the measurementlight L2 back-scattered from the light transmitted through the skintissue and diffused, using the light receiving element 130 via thesecond light receiving part 119.

A light (short pulsed light) from the first input part 116 is incidenton the liquid tank 114 filled with the liquid Q, which is the referencematerial, for example, water. The reference light L1 transmitted throughthe liquid Q is detected by the light receiving element 130 via thefirst light receiving part 117 to thereby measure an absorbance aftertransmission through the water.

The calculation of the glucose concentration in the skin tissue isperformed from the absorbance after back-scattering at the living bodytissue and the absorbance after transmission through the water, whichare obtained using the above method. For example, the operational unit150 includes a measuring object absorbance calculation unit (anabsorbance calculation device) 151 and a concentration calculation unit(a concentration calculation device) 152. The measuring objectabsorbance calculation unit (the absorbance calculation device) 151obtains an absorbance of the living body tissue with respect to thewater that is the reference material. The absorbance of the living bodytissue is obtained using, for example, Equation (1):

[Equation 1]

μ_(a) l−μ _(aw) d=μ _(a1) V ₁ l+μ _(a2) V ₂ l+ . . . +μ _(an) V _(n) l+μ_(aw)(V _(w) l−d)   (1)

In Equation (1), μ_(a) denotes the absorption coefficient of themeasuring object (the arm part), μ_(a1), μ_(a2) and μ_(an) denoteabsorption coefficients of components 1, 2 and n of the measuringobject, μ_(aw) denotes the absorption coefficient of the water, V₁, V₂,and V_(n) denote concentrations (volume fraction) of the components 1, 2and n of the measuring object, l denotes an average value of an opticalpath length of measuring object, d denotes an optical path length of thewater, and V_(wl) denotes a concentration (volume fraction) of the waterin the living body tissue.

In Equation (1), the absorption coefficients of the components of themeasuring object, the absorption coefficient of the water, theconcentrations (volume fraction) of the components of the measuringobject, and a concentration (volume fraction) of the water in the livingbody tissue may be replaced with molar absorption coefficients of thecomponents of the measuring object, a molar absorption coefficient ofthe water, molar concentrations of the components of the measuringobject, and a molar concentration of the water in the living bodytissue, respectively.

It is preferable that an optical path length d for the water arranged onthe reference optical path be a value close to a value obtained bymultiplying an average value l of an optical path length for themeasuring object by a volume concentration V_(wl) of the water in theliving body tissue. This is because the resultant absorbance decreasesand an influence of the water occupying most of the living body tissuecan be reduced for highly accurate measurement. l may be calculatedusing, for example, the Monte Carlo method according to a scatteringcoefficient of the living body tissue in advance and an average value ofthe measuring object may be used as V_(w) to determine d.

Simulation using the Monte Carlo method, for example, is performed asfollows:

First, photons (beam) are used as a model of an irradiation light andirradiated to a skin model to perform calculation. The photonsirradiated to the skin model move in the skin model. In this case, adistance L and a direction θ to a next point to which the photonsproceed are determined by a random number R. Calculation of the distanceL to the next point to which the photons proceed is performed using thefollowing Equation (2):

[Equation 2]

L=ln(R/μ _(s))   (2)

In Equation (2), ln(A) indicates a natural logarithm of A. μ_(s) denotesa scattering coefficient of the s-th layer (any one of an epidermallayer, a dermal layer, and a subcutaneous tissue layer) of the skinmodel. Calculation of the direction θ to the next point to which thephotons proceed is performed by the following Equation (3).

$\begin{matrix}\lbrack {{Equation}\mspace{14mu} 3} \rbrack & \; \\{\theta = {\cos^{- 1}\lbrack {\frac{1}{2g}\{ {1 + g^{2} - ( \frac{1 - g^{2}}{1 + g - {2{gR}}} )^{2}} \}} \rbrack}} & (3)\end{matrix}$

In Equation (3), g denotes an anisotropy parameter that is an average ofa cosine of a scattering angle and the anisotropy parameter of the skinis about 0.9.

The calculations of Equations (2) and (3) are iteratively performed perunit time. Accordingly, the movement path of the photons from the outputsurface 118 a to the input surface 119 a can be calculated. Also, thecalculation of the movement distance may be performed on a plurality ofphotons. For example, the movement distance of 10⁸ photons iscalculated.

FIG. 5 is a graph showing an example of an optical propagation pathlength distribution of the layers of a living body tissue (skin).

In FIG. 5, a horizontal axis indicates an elapsed time from theirradiation of photons, and a vertical axis indicates a logarithm of theoptical path length. Movement paths of photons reaching the lightreceiving element are classified for each layer through which themovement path passes, and an average length of the movement path of thephotons reaching per unit time is calculated for each classified layer.Accordingly, the optical propagation path length distributions of therespective layers of the skin as shown in FIG. 4 can be calculated.

FIG. 6 is a graph showing an example of a time-resolved waveform.

In FIG. 6, a horizontal axis indicates an elapsed time from theirradiation of photons, and a vertical axis indicates the detectedphoton number by the light receiving element. The number of the photonsreaching the light receiving element per unit time is calculated.Accordingly, a time-resolved waveform of the skin model as shown in FIG.5 can be calculated.

Through the process described above, the optical propagation path lengthdistribution and the time-resolved waveform of the skin model arecalculated for a plurality of wavelengths. In this case, the opticalpropagation path length distribution and the time-resolved waveform maybe calculated for a wavelength at which orthogonality of absorptionspectra of main components (e.g., water, protein, lipid, glucose) of theskin becomes higher.

FIG. 7 is a graph showing absorption spectra of main components of theskin.

In FIG. 7, a horizontal axis indicates a wavelength of an irradiationlight, and a vertical axis indicates an absorption coefficient.Referring to FIG. 7, an absorption coefficient of glucose is maximizedwhen the wavelength is 1600 nm, and an absorption coefficient of wateris maximized when the wavelength is 1450 nm. Accordingly, for example,the optical propagation path length distribution and the time-resolvedwaveform may be calculated for the wavelengths 1450 nm or 1600 nm atwhich orthogonality of the absorption spectra of the main components ofthe skin becomes higher.

The concentration is obtained by the concentration calculation unit (theconcentration calculation device) 152. The concentration calculation canbe performed by solving Equation (1) as simultaneous equationscorresponding to a plurality of wavelengths. The obtained glucoseconcentration in the living body tissue is displayed and output on theconcentration display unit 160 as a blood sugar level.

Further, the concentration of the living body tissue may be obtainedusing, for example, multi-variate analysis such as main-componentregression analysis.

As described above, according to the concentration determinationapparatus and the concentration determination method of the presentinvention, the liquid (e.g., water) that is the reference material isstored in the liquid tank (storage body), which stores the liquid, andthe absorbance of the reference light transmitted through the liquid isreferenced with respect to the absorbance of the measurement lightback-scattered from the living body tissue that is the measuring object,thereby obtaining an accurate absorbance without being affected by theliquid (e.g., water) contained in the measuring object.

Further, the temperature control plate having excellent thermalconductivity is formed in at least part of the liquid tank (storagebody) that contacts the measuring object. Accordingly, the temperatureof the water in the liquid tank rises due to the body temperature of theliving body tissue that is the measuring object, for example, the humanbody, through the temperature control plate, such that the temperatureof the water can be rapidly the same as the temperature of the livingbody tissue. An absorption characteristic of the water is sensitive to atemperature, as is well known. However, as in the present embodiment,the temperature of the liquid that is the reference material becomes thesame as the temperature of the living body tissue that is the measuringobject (a thermal equilibrium state) and then the absorbance ismeasured, thereby eliminating an error caused by an influence of waterin the living body tissue due to a temperature change and performing anaccurate concentration determination for the measured material.

Second Embodiment

FIG. 8 is a schematic block diagram showing a configuration of a bloodsugar level measurement apparatus in a second embodiment.

In the second embodiment, a light receiving element 231 for receiving areference light and a light receiving element 232 for receiving ameasurement light are independently formed, unlike the first embodimentdescribed above. An arithmetic unit 250 includes a measuring objectabsorption coefficient calculation unit 251, a volume fractioncalculation unit 252, a concentration unit conversion unit 253, anoptical path length information storage unit (an optical path lengthinformation measurement unit) 254, and a component absorptioninformation storage unit 255.

In the blood sugar level measurement apparatus 200 of the secondembodiment, an absorption coefficient of the measuring object withrespect to water (liquid), which is a reference material, is calculatedfrom a measurement light as a back-scattered light from the living bodytissue that is the measuring object. An optical path length d for thewater is set to l. l can be calculated, for example, using a Monte Carlomethod in advance, as in the first embodiment. When l=d, Equation (1)described above may be replaced with Equation (4) shown below. Whensimultaneous equations for a plurality of wavelengths are solved usingEquation (4), the number of wavelength data equations is reduced by oneas compared to the first embodiment, which can simplify a procedure(process) of a concentration calculation process.

[Equation 4]

μ_(a)−μ_(aw)=(μ_(a1)−μ_(aw))V ₁+(μ_(a2)−μ_(aw))V ₂+ . . .+(μ_(an)−μ_(aw))V _(n) where V ₁ +V ₂ + . . . +V _(n) +V _(w)=1   (4)

Third Embodiment

FIG. 9 is a schematic block diagram of a configuration of a blood sugarlevel measurement apparatus in a third embodiment.

In the third embodiment, a light receiving element 341 for receiving areference light and a light receiving element 342 for receiving ameasurement light are independently formed. Further, an arithmetic unit350 includes a water absorption coefficient calculation unit 351, ameasuring object absorption coefficient calculation unit 352, acomponent volume fraction calculation unit 353, a concentration unitconversion unit 354, an optical path length information storage unit (anoptical path length information measurement unit) 355, and a componentabsorption information storage unit 356.

In the blood sugar level measurement apparatus 300 of the thirdembodiment, an absorption coefficient of water (liquid) that is areference material and an absorption coefficient of a living body tissuethat is a measuring object are individually calculated, unlike the firstembodiment and the second embodiment. The absorption coefficient of thewater is calculated by calculating the absorbance of the water from asignal of the light receiving element 341 of the reference lighttransmitted through the water and using optical path length informationof the water.

Similarly, in the calculation of the absorption coefficient of themeasuring object (the living body tissue), an absorbance of the livingbody tissue is calculated from a signal of the light receiving element342 of the measurement light that is a back-scattered light from theliving body tissue. The calculation of the absorption coefficient of themeasuring object can be performed by obtaining an absorption coefficientof a portion of the target through time-resolved measurement. If theabsorption coefficients of the water and the measuring object areobtained, the calculation of the component concentration may beperformed using the same method as in the first embodiment and thesecond embodiment.

Fourth Embodiment

FIG. 10A is a cross-sectional view showing a configuration of a bodypart of a blood sugar level measurement apparatus in a fourthembodiment. FIG. 10B is a plan view of the body part shown in FIG. 10Awhen viewed from above.

In the fourth embodiment, for example, a hollow liquid tank (a storagebody) 514 that liquid (reference material) Q can be injected into andstored in is formed in a first measurement area 513 a of the body part511 in the blood sugar level measurement apparatus 500. In the firstmeasurement area 513 a, a first input part 516 is formed in a topsurface 511 b at an opposite side from a bottom surface 511 a of thebody part 511 in contact with a living body tissue that is a measuringobject so that an output surface 516 a of the first input part 516 isexposed to an inner surface of the liquid tank 514. The first input part516 is, for example, optically connected to a light source.

A first light receiving part 517 is formed to be aligned with the firstinput part 516 so that an input surface 517 a thereof is exposed to theinner surface of the liquid tank 514. The first light receiving part 517is optically connected to a light receiving element.

An optical reflection film (reflector) 530 is formed to face the outputsurface 516 a and the input surface 517 a on a bottom surface of theliquid tank 514 that is the bottom surface 511 a of the body part 511.According to the above-described configuration, a light output from theoutput surface 516 a of the first input part 516 is transmitted throughthe liquid (water) Q stored in the liquid tank 514 and reaches theoptical reflection film (reflector) 530. Also, the light is reflected bythe optical reflection film (reflector) 530. The reflected light istransmitted through the liquid (water) Q again and incident on the inputsurface 517 a of the first light receiving part 517.

The first input part 516 may be formed to irradiate light at apredetermined angle with respect to the bottom surface 511 a of the bodypart 511 in advance such that the light reflected by the opticalreflection film (reflector) 530 can be accurately incident on the inputsurface 517 a of the first light receiving part 517. For the opticalreflection film (reflector) 530, a liquid contact surface 570 b of atemperature control plate 570 may be used as an optical reflectivesurface.

Alternatively, a scattering material such as intralipid may be mixedwith the liquid (water) that is the reference material to obtain ascattering characteristic and a back-scattered light may be detectedusing the light receiving element, instead of forming theabove-described optical reflection film (reflector).

Fifth Embodiment

FIG. 11 is a cross-sectional view showing a configuration of a body partof a blood sugar level measurement apparatus in a fifth embodiment.

In the fifth embodiment, for example, a hollow liquid tank (a storagebody) 614 that liquid (reference material) Q can be injected into andheld in is formed in a first measurement area 613 a of a body part 611in the blood sugar level measurement apparatus 600. A temperaturecontrol plate 670 is formed at a side of a bottom surface among wallsurfaces partitioning the liquid tank (storage body) 614. In the presentembodiment, the temperature control plate 670 is formed of a Peltierelement. The Peltier element is formed of, for example, a metalelectrode, a p-type semiconductor, and an n-type semiconductor that arealternately connected between upper and lower heat sinks.

When DC current flows into a junction between two types of metals in theabove-described Peltier element, the one surface absorbs the heat andheat emission occurs from the opposite surface due to a Peltier effectby which heat moves from one metal to the other metal, which is wellknown.

In the Peltier element, when there is a temperature difference betweenthe one metal and the other metal, a potential difference is generatedbetween the two types of metals (a Seebeck effect), as is well known.Using this operation, it is possible to detect the temperaturedifference by measuring the potential difference between the two typesof metals.

Using the above-described effect, in the temperature control plate (atemperature detection device or a temperature control device) 670 formedof the Peltier element, a potential difference between a closelycontacted surface 670 a closely contacted to a surface of an arm part Wof a human body that is the living body tissue and a liquid contactsurface 670 b in contact with the liquid (reference material) Q isdetermined by a potential difference detection device 675. Also, whenthere is a potential difference between the closely contacted surface670 a and the liquid contact surface 670 b, a circuit connected to thetemperature control plate (the temperature detection device or thetemperature control device) 670 is switched to a voltage applying device676.

Also, a voltage from the voltage applying device 676 is applied to thetemperature control plate (the temperature detection device or thetemperature control device) 670, for example, to heat the liquid contactsurface 670 b and warm the liquid (reference material) Q. Also, at anytime, the circuit is switched to the voltage detection device 675 tomeasure a potential difference between the closely contacted surface 670a and the liquid contact surface 670 b, and the liquid contact surface670 b may be heated until the potential difference between the closelycontacted surface 670 a and the liquid contact surface 670 b iseliminated.

As a Peltier element functioning as both the temperature detectiondevice and the temperature control device is used as the temperaturecontrol plate 670, even when there is a temperature difference betweenthe living body tissue that is the measuring object and the liquid (areference material), the temperature difference can be rapidlyeliminated and an accurate concentration determination can be rapidlyperformed without being affected by a temperature change.

While the preferred embodiments of the present invention have beendescribed above, the present invention is not limited to theembodiments. Addition, omission, substitution, and other modificationmay be made to the configuration of the present invention withoutdeparting from the spirit and scope of the present invention. Thepresent invention is not limited by the above description but limitedonly by the claims.

100: concentration determination apparatus (blood sugar levelmeasurement apparatus), 114: liquid tank (storage body), 115:temperature detection device, 116: first input part, 117: first lightreceiving part, 118: second input part, 119: second light receivingpart, 151: measuring object absorbance calculation unit (absorbancecalculation device), 152: concentration calculation unit (concentrationcalculation device), 170: temperature control plate, 170 a: closelycontacted surface, 170 b: liquid contact surface.

1. A concentration determination apparatus comprising: a storage bodythat holds liquid, a temperature control plate constituting the storagebody and having one surface forming a closely contacted surface which isclosely contacted to a living body tissue and another surface forming aliquid contact surface brought into contact with the liquid, a firstinput part that causes a first incident light to be incident on thestorage body, a first light receiving part that receives a referencelight transmitted through the liquid from the first input part, a secondinput part that causes a second incident light to be incident on theliving body tissue, a second light receiving part that receives ameasurement light from the second input part via the living body tissue,a temperature detection device that detects a temperature of the liquidand a temperature of the living body tissue, an absorbance calculationdevice that detects an absorbance of the liquid and an absorbance of theliving body tissue based on a light intensity of the reference light anda light intensity of the measurement light, and a concentrationcalculation device that compares the absorbance of the liquid with theabsorbance of the living body tissue and calculates a concentration of ameasured component contained in the living body tissue.
 2. Theconcentration determination apparatus according to claim I, wherein theliquid is a liquid having a scattering characteristic.
 3. Theconcentration determination apparatus according to claim 2, wherein theliquid is water or liquid corresponding to body fluid whose componentconfiguration is obvious.
 4. The concentration determination apparatusaccording to claim 1, wherein the temperature control plate includes athermal conductor that causes the body temperature of the living bodytissue and the liquid temperature of the liquid to be heat-exchangedwith each other.
 5. The concentration determination apparatus accordingto claim 1, wherein the storage body further includes a reflector thatreflects the first incident light incident from the first input part tothe first light receiving part.
 6. The concentration determinationapparatus according to claim 1, further comprising a light source unitincluding a plurality of light sources.
 7. The concentrationdetermination apparatus according to claim 1, wherein the storage bodyfurther comprises a temperature control device that heats or cools theliquid.
 8. The concentration determination apparatus according to claim1, further comprising a light source unit including a light source, anda spectroscopic device that divides light irradiated from the lightsource toward the first input part and the second input part.
 9. Theconcentration determination apparatus according to claim 1, furthercomprising one light receiving element that measures both the lightintensity of the reference light incident on the first light receivingpart and the light intensity of the measurement light incident on thesecond light receiving part.
 10. The concentration determinationapparatus according to claim 1, wherein an optical path length for thereference light from the first input part to the first light receivingpart is set to be the same as an optical path length for the measurementlight from the second input part to the second light receiving part. 11.A concentration determination method using a concentration determinationapparatus comprising a storage body that holds liquid, a temperaturecontrol plate constituting the storage body and having one surfaceforming a closely contacted surface which is closely contacted to aliving body tissue and the other surface forming a liquid contactsurface brought into contact with the liquid, a first input part thatcauses a first incident light to be incident on the storage body, afirst light receiving part that receives a reference light transmittedthrough the liquid from the first input part, a second input part thatcauses a second incident light to be incident on the living body tissue,a second light receiving part that receives a measurement light from thesecond input part via the living body tissue, a temperature detectiondevice that detects a temperature of the liquid and a temperature of theliving body tissue, an absorbance calculation device that detects anabsorbance of the liquid and an absorbance of the living body tissuebased on a light intensity of the reference light and a light intensityof the measurement light, and a concentration calculation device thatcompares the absorbance of the liquid with the absorbance of the livingbody tissue and calculates a concentration of a measured componentcontained in the living body tissue, wherein: the measurement light islight from the second incident light back-scattered in the living bodytissue, and the method comprises processes of: equilibrating thetemperatures so that a difference between the body temperature of theliving body tissue and the liquid temperature of the liquid is within0.1° C.; measuring the absorbance of the liquid based on the lightintensity of the reference light; measuring the absorbance of the livingbody tissue based on the light intensity of the measurement light; andusing the absorbance of the liquid as a reference and calculating theconcentration of the measured component contained in the living bodytissue from the absorbance of the living body tissue.
 12. Theconcentration determination method according to claim 11, wherein thefirst incident light and the second incident light are short pulsedlights.